Methyl indole-6-carboxylate → 6-Hydroxymethylindole

HRID 351592Notes

Reaction equation

HRID 351592 reaction equation
C[O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[CH:10][NH:11]2)=[CH:7][CH:6]=1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[OH:2][CH2:3][C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[CH:10][NH:11]2)=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 639844Methyl indole-6-carboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 27734596-HydroxymethylindoleYield 95.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of indole-6-carboxylic acid methyl ester (20.0 g, 114 mmol) in anhydrous tetrahydrofuran (1.6 L) stirring under nitrogen at room temperature was added carefully lithium aluminum hydride (8.7 g, 230 mmol) while purging with nitrogen. Following this addition, the reaction mixture was stirred at room temperature for 3 hours and was then cooled to 0° C. This mixture was treated sequentially with water (9 mL), 15% sodium hydroxide (9 mL), and additional water (25 mL). The resulting suspension was filtered and the filtrate concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with 30%-60% ethyl acetate in hexanes. Fractions containing product were combined and concentrated under reduced pressure to provide 16.0 g (95%) of the desired compound as an off-white solid.

Workup

  1. customwhile purging with nitrogen
  2. additionthis addition
  3. temperaturewas then cooled to 0° C
  4. additionThis mixture was treated sequentially with water (9 mL), 15% sodium hydroxide (9 mL), and additional water (25 mL)
  5. filtrationThe resulting suspension was filtered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. washeluting with 30%-60% ethyl acetate in hexanes
  8. additionFractions containing product
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c183b807a749403db671be09f5f29f83
Source dataset
uspto-grants-2004_06
Patent number
US06743785B2

Reaction notes

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